Clinical and Biomarker Responses to BI 655064, an Antagonistic Anti-CD40 Antibody, in Patients With Active Lupus Nephritis: A Randomized, Double-Blind, Placebo-Controlled, Phase II Trial
Issued Date
2023-01-01
Resource Type
ISSN
23265191
eISSN
23265205
Scopus ID
2-s2.0-85168331947
Pubmed ID
37192040
Journal Title
Arthritis and Rheumatology
Rights Holder(s)
SCOPUS
Bibliographic Citation
Arthritis and Rheumatology (2023)
Suggested Citation
Jayne D.R., Steffgen J., Romero-Diaz J., Bajema I., Boumpas D.T., Noppakun K., Amano H., Gomez H.M., Satirapoj B., Avihingsanon Y., Chawanasuntorapoj R., Madero M., Naumnik B., Recto R., Fagan N., Revollo I., Wu J., Visvanathan S., Furie R. Clinical and Biomarker Responses to BI 655064, an Antagonistic Anti-CD40 Antibody, in Patients With Active Lupus Nephritis: A Randomized, Double-Blind, Placebo-Controlled, Phase II Trial. Arthritis and Rheumatology (2023). doi:10.1002/art.42557 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/88853
Title
Clinical and Biomarker Responses to BI 655064, an Antagonistic Anti-CD40 Antibody, in Patients With Active Lupus Nephritis: A Randomized, Double-Blind, Placebo-Controlled, Phase II Trial
Author's Affiliation
Siriraj Hospital
Department of Medicine
Angeles University Foundation
Donald and Barbara Zucker School of Medicine at Hofstra/Northwell
Boehringer Ingelheim Pharmaceuticals, Inc.
Faculty of Medicine, Chiang Mai University
Uniwersytet Medyczny w Bialymstoku
Attikon University Hospital
Boehringer Ingelheim Pharma GmbH & Co. KG
Instituto Nacional de Cardiologia Ignacio Chavez
Juntendo University School of Medicine
Instituto Nacional de la Nutrición Salvador Zubiran
Phramongkutklao College of Medicine
Universitair Medisch Centrum Groningen
Faculty of Medicine, Chulalongkorn University
Mary Mediatrix Medical Center
Department of Medicine
Angeles University Foundation
Donald and Barbara Zucker School of Medicine at Hofstra/Northwell
Boehringer Ingelheim Pharmaceuticals, Inc.
Faculty of Medicine, Chiang Mai University
Uniwersytet Medyczny w Bialymstoku
Attikon University Hospital
Boehringer Ingelheim Pharma GmbH & Co. KG
Instituto Nacional de Cardiologia Ignacio Chavez
Juntendo University School of Medicine
Instituto Nacional de la Nutrición Salvador Zubiran
Phramongkutklao College of Medicine
Universitair Medisch Centrum Groningen
Faculty of Medicine, Chulalongkorn University
Mary Mediatrix Medical Center
Other Contributor(s)
Abstract
Objective: To characterize its dose-response relationship, BI 655064 (an anti-CD40 monoclonal antibody) was tested as an add-on to mycophenolate and glucocorticoids in patients with active lupus nephritis (LN). Methods: A total of 121 patients were randomized (2:1:1:2) to receive placebo or BI 655064 120, 180, or 240 mg and received a weekly loading dose for 3 weeks followed by dosing every 2 weeks for the 120 and 180 mg groups, and 120 mg weekly for the 240 mg group. The primary endpoint was complete renal response (CRR) at week 52. Secondary endpoints included CRR at week 26. Results: A dose-response relationship with CRR at week 52 was not shown (BI 655064 120 mg, 38.3%; 180 mg, 45.0%; 240 mg, 44.6%; placebo, 48.3%). At week 26, 28.6% (120 mg), 50.0% (180 mg), 35.0% (240 mg), and 37.5% (placebo) achieved CRR. The unexpected high placebo response prompted a post hoc analysis evaluating confirmed CRR (cCRR, at weeks 46 and 52). cCRR was achieved in 22.5% (120 mg), 44.3% (180 mg), 38.2% (240 mg), and 29.1% (placebo) of patients. Most patients reported ≥1 adverse event (BI 655064, 85.7–95.0%; placebo, 97.5%), most frequently infections and infestations (BI 655064 61.9–75.0%; placebo 60%). Compared with other groups, higher rates of serious (20% vs. 7.5–10%) and severe infections (10% vs. 4.8–5.0%) were reported with 240 mg BI 655064. Conclusion: The trial failed to demonstrate a dose-response relationship for the primary CRR endpoint. Post hoc analyses suggest a potential benefit of BI 655064 180 mg in patients with active LN.